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Profilo Immunoistochimico di Citochine Infiammatorie e Fattori di Crescita nell'Occhio Umano
Full text linkThe aim of this experimental thesis focuses on the study of eye diseases related to the involvement of growth factors, of inflammatory cytokines in chronic-inflammatory, and of tissue remodeling. Particular emphasis has been addressed to the physiopathology of the eye surface and the complex relationships existing between cells and mediators in the immune response. Furthermore, the research has been directed to molecular events that control these biological responses. The lost in regulation of the inflammatory processes corresponds to the loss of control of the production/action of cytokines followed by the onset of inflammatory or autoimmune pathologies.
Immunohistochemical technique has been performed in order to evaluate the physiopathological behaviour of inflammatory cytokines and of some growth factors (TGF-b1, IL-1b, IL-6, TNF-a and VEGF) located in the ocular tissues. Samples were obtained from human patients affected by glaucoma, diabetic retinopathy and macular degeneration. Our main purpose was to assess the levels of expression and localization of pro-inflammatory cytokines by immunohistochemistry in order to identify their involvement in the pathology, assuming for them a role in the modulation of these factors as a potential therapeutic target. Our study has shown an imbalance between pro- and anti-inflammatory cytokine plays a key role in the pathogenesis of retinal diseases. This disproportion within a complex regulatory network is related to some immunological processes that promote autoimmunity, chronic inflammation and / or tissue destruction. We were able to confirm that the inflammatory process involves a complex cascade of molecular and cellular biological signals, altering the physiological responses of the ocular tissues. The transmission electron microscopy investigation (TEM) showed that at the site of the lesion cells the probable release of molecular signals produces changes in the affected area: dilation of blood vessels resulting in increased blood flow and vascular permeability, exudation of fluid containing proteins such as immunoglobulins and invasion by leukocytes. It is well known that chronic and prolonged inflammation is a fundamental feature in some diseases such as atherosclerosis, obesity, diabetes, rheumatoid arthritis, asthma and various types of cancer. These diseases are strictly connected with their ocular manifestations: diabetic retinopathy, scleritis, uveitis, dry eye syndrome and ocular tumours. It should be noticed that pharmacological and clinical advances occur in areas apparently distant from application in ophthalmology, but they should be potentially used also in the ocular field by a translational application. Since many ocular tissues have a immune-privileged system to protect the delicate visual apparatus, the control of the acute inflammation is regulated by the same pathways and mediators that manage inflammatory responses in other organs. These scientific informations not only provide further support to the chronic inflammation, that plays a significant role in the pathogenesis of diabetic retinopathy, but also suggest that the inflammatory process is active even before retinopathy (diabetic and/or proliferative) is clinically diagnosed. Therefore, the alteration of the profile of some cytokines might be useful both as a predictive marker as well as an important target for the development of new therapeutic treatments.
A novel pharmacological approach to treat eye inflammation may be represented by progress in the cellular therapy. In recent years, research has been devoted to the development of cell therapy applied to eye diseases producing a remarkably increased risk of visual impairment. Recently, cellular therapy has evolved into two research pathways: one finalized to a remodeling of the structure and the relative functions of specific tissues using stem cells; the other one has been focused on the restore of the immunological homeostasis controlling the harmful effects caused by inflammatory diseases
The kinesin Eg5 inhibitor K858 exerts antiproliferative and proapoptotic effects and attenuates the invasive potential of head and neck squamous carcinoma cells
Full text linkOur group recently demonstrated that K858, an inhibitor of motor kinesin Eg5, has important antiproliferative and apoptotic effects on breast cancer, prostatic cancer, melanoma and glioblastoma cells. Since high levels of kinesin Eg5 expression have been correlated with a poor prognosis in laryngeal carcinoma, we decided to test the anticancer activity of K858 toward this tumor, which belongs to the group of head and neck squamous cell carcinomas (HNSCCs). These cancers are characterized by low responsiveness to therapy. The effects of K858 on the proliferation and assembly of mitotic spindles of three human HNSCC cell lines were studied using cytotoxicity assays and immunofluorescence for tubulin. The effect of K858 on the cell cycle was analyzed by FACS. The expression levels of cyclin B1 and several markers of apoptosis and invasion were studied by Western blot. Finally, the negative regulation of the malignant phenotype by K858 was evaluated by an invasion assay. K858 inhibited cell replication by rendering cells incapable of developing normal bipolar mitotic spindles. At the same time, K858 blocked the cell cycle in the G2 phase and induced the accumulation of cytoplasmic cyclin B and, eventually, apoptosis. Additionally, K858 inhibited cell migration and attenuated the malignant phenotype. The data described confirm that kinesin Eg5 is an interesting target for new anticancer strategies and suggest that this compound may be a powerful tool for an alternative therapeutic approach to HNSCCs
Human lymphatic mesenteric vessels. Morphology and possible function of aminergic and NPY-ergic nerve fibers
No full textThe lymphatic vessels have been studied in different organs from a morphological to a clinical point of view. Nevertheless, the knowledge of the catecholaminergic control of the lymphatic circulation is still incomplete. The aim of this work is to study the presence and distribution of the catecholaminergic and NPY-ergic nerve fibers in the whole wall of the human mesenteric lymphatic vessels in order to obtain knowledge about their morphology and functional significance
The emerging role of epigenetics in human autoimmune disorders
Full text linkEpigenetic pathways play a pivotal role in the development and function of the immune system. Over the last
decade, a growing body of studies has been published out seeking to explain a correlation between epigenetic
modifications and the development of autoimmune disorders. Epigenetic changes, such as DNA methylation,
histone modifications, and noncoding RNAs, are involved in the pathogenesis of autoimmune diseases mainly by
regulating gene expression. This paper reviews the importance of epigenetic alterations during the development of
the most prevalent human autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis
(RA), systemic sclerosis (SSc), Sjogren’s syndrome (SS), autoimmune thyroid diseases (AITD), and type 1 diabetes
(T1D), aiming to provide new insights in the pathogenesis of autoimmune diseases and the possibility to develop
novel therapeutic approaches targeting the epigenome
Corrigendum: VEGF in nuclear medicine: Clinical application in cancer and future perspectives (Review) (International Journal of Oncology (2016) 49 (437-447) DOI:10.3892/ijo.2016.3553)
No full textFollowing the publication of this article, after having re-examined our manuscript, we noted an error in the acknowledgements section, as regards the funding of our study. The correct version of acknowledgements section is shown below: Acknowledgements This study was supported by the Ministry of Health and Fondazione Roma and by NOBILE S.p.A. Thanks are also due to REGIONE LAZIO Prot. FILAS-RU-2014 - 1020 (E.A.). [the original article was published in the International Journal of Oncology 49: 437-447, 2016; DOI: 10.3892/ijo.2016.3553]
Biochemical functions and clinical characterizations of the sirtuins in diabetes-induced retinal pathologies
Full text linkDiabetic retinopathy (DR) is undoubtedly one of the most prominent causes of blindness
worldwide. This pathology is the most frequent microvascular complication arising from diabetes,
and its incidence is increasing at a constant pace. To date, the insurgence of DR is thought to be
the consequence of the intricate complex of relations connecting inflammation, the generation of
free oxygen species, and the consequent oxidative stress determined by protracted hyperglycemia.
The sirtuin (SIRT) family comprises 7 histone and non-histone protein deacetylases and mono
(ADP-ribosyl) transferases regulating different processes, including metabolism, senescence, DNA
maintenance, and cell cycle regulation. These enzymes are involved in the development of various
diseases such as neurodegeneration, cardiovascular pathologies, metabolic disorders, and cancer.
SIRT1, 3, 5, and 6 are key enzymes in DR since they modulate glucose metabolism, insulin sensitivity,
and inflammation. Currently, indirect and direct activators of SIRTs (such as antagomir, glycyrrhizin,
and resveratrol) are being developed to modulate the inflammation response arising during DR. In
this review, we aim to illustrate the most important inflammatory and metabolic pathways connecting
SIRT activity to DR, and to describe the most relevant SIRT activators that might be proposed as new
therapeutics to treat DR
Ultrastructure of neurovascular changes in human diabetic retinopathy
Full text linkThe previous concept regarding diabetic retinopathy assigned a primary role to hyperglycemia-induced microvascular alterations, while neuronal and glial abnormalities were considered to be secondary to either ischemia or exudation. The aim of this study was to reveal the potential role of neuronal and glial cells in initial and advanced alterations of the retinopathy in human type 2 diabetes. Electron microscopy and histochemical studies were performed on 38 surgically removed human eyes (28 obtained from diabetic patients and 10 from non-diabetic patients). Morphometric analysis of basement membrane material and lipids was performed. An accumulation of metabolic by-products was found in the capillary wall with aging: this aspect was significantly more pronounced in diabetics. Müller glial cells were found to contribute to alterations of the capillary wall and to occlusion, as well as to the development of proliferative retinopathy and cystoid degeneration of the retina. Our results showed morphological evidence regarding the role of neuronal and glial cells in the pathology of diabetic retinopathy, prior and in addition to microangiopathy. These morphological findings support a neurovascular pathogenesis at the origin of diabetic retinopathy, thus the current treatment approach should be completed by neuroprotective measures
Immunohistochemical profile of VEGF, PGE2 and TGF-β in inflammatory tenosynovitis of carpal tunnel syndrome
No full textCellular Immuno-Profile in Septic Human Host: A Scoping Review
Full text linkInnate and adaptive immune system cells play a critical role in the host response to sepsis. Sepsis is a life-threatening disease characterized by apoptosis-induced depletion of immune cells and immunodepression, which contribute to morbidity and mortality. Many alterations in the expression of surface markers of neutrophils and monocytes have been described in septic patients. The aim of this study was to inspect the recently published literature to inform the clinician about the most up-to-date techniques for the study of circulating leukocytes. The impact on cell phenotypes and on the function of leukocytes of extracorporeal and non-blood purification treatments proposed for sepsis were also analyzed. We conducted a systematic review using Pubmed/Medline, Ovid/Willey, the Cochrane Library, the Cochrane Controlled Trials Register, and EMBASE, combining key terms related to immunological function in sepsis and selected the most relevant clinical trials and review articles (excluding case reports) published in the last 50 years. The most important alteration in neutrophils during sepsis is that they activate an anti-apoptotic survival program. In septic monocytes, a reduced characteristic expression of HLA-DR is observed, but their role does not seem to be significantly altered in sepsis. As regards adaptive immunity, sepsis leads to lymphopenia and immunosuppression in patients with septic shock; this process involves all types of T cells (CD4, CD8 and Natural Killer), except for regulatory T cells, which retain their function. Several promising therapies that target the host immune response are currently under evaluation. During the worldwide pandemic caused by SARS-CoV-2, it was useful to study the “cytokine storm” to find additional treatments, such as the oXiris® filter. This therapy can decrease the concentration of inflammatory markers that affect the severity of the disease
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